tbuckley/cabot-search huggingface dataset:
Impact and engagement of a virtual platform to provide equitable oncology education globally.
Authors: Yan Leyfman, Shubhadarshini Pawar, Muskan Joshi, Maduri Balasubramanian, William B. Wilkerson, Gayathri P. Menon, Alexandra Van de Kieft, Sean Jackewicz, Rabab H. Abbas, Chandler H. Park
Journal: Journal of Clinical Oncology (2023)

11019 Background: Social media has emerged as a powerful outlet for the dissemination of medical information, especially in resource-limited regions, due to its mass global reach. However, misinformation has presented an unexpected detriment to public health on a global scale. To address this, MedNews Week (MNW), a free, virtual educational platform streamed on most social media platforms was developed to provide global oncology education through biweekly programming. Its leading show, Keynote Conference, features live virtual presentations from oncology’s premier global leaders discussing the latest developments in the field before a mainstream global audience. The aim of this study was to assess the worldwide reach and impact of this cost-free, virtual oncology education platform. Methods: From January 2022 to February 2023, MNW hosted 33 global leaders as Keynote Speakers discussing the latest developments in oncology. Viewership, impressions, and outreach data were collected from MNW’s social media accounts and Tweepmaps. Data was analyzed to assess MNW’s global reach and engagement and stratified based on engagement sentiment, gender, age group, and occupation. Results: During this period, MNW produced a healthcare social grasp score of 64% and generated over 64,000 Twitter impressions engaging 1.9 million viewers over 13 months in the US, UK, Ireland, India, France, and 16 lower socioeconomic (SE) countries and 99 cities. Most of the followers were from non-healthcare fields with more males than females (Table). Those who engaged conveyed positive sentiments (64%) contributing to a viewership increase from 47,589 (6 months) to 61,539 (1 year), where 60% of the audience was found to originate from lower SE regions globally. Conclusions: MNW has demonstrated an ability to attract and sustain a diverse, global, growing mainstream audience. Given MNW’s continued growth, it provides a proof-of-concept model to engage and disseminate medical information to mainstream audiences. The platform’s ability to showcase global leaders to mainstream audiences gratuitously, especially in lower SE regions that have been historically underserved, offers a practical approach to combat educational inequity. Consequently, such a platform has demonstrated great potential to positively impact global oncology education. Demographics of MedNews Week’s audience. [Table: see text]
Publication trends in sarcoma research: A bibliometric analysis.
Authors: Dino Fanfan, Oreoluwa Olorunlogbon, Yandhira Thalia Figueroa, Jonathan C. Trent
Journal: Journal of Clinical Oncology (2023)

e23530 Background: Sarcomas are rare primary malignant tumors originating from connective tissue, worldwide research trends on this topic are unclear. We conducted a bibliometric analysis of the 100 most influential articles on sarcoma. Methods: We sourced the literature published in academic journals indexed by the Scopus Database. Using the key words “sarcoma,” “soft-tissue tumor,” “bone sarcoma,” “soft-tissue sarcoma,” “connective tissue malignancy.” A list of the 100 most-cited articles were extracted and sorted by number of citations, excluding articles related to Kaposi’s Sarcoma. The papers were checked independently by our authors for accuracy of topic. R was used to extract the publishing journal, year of publication, country of origin, affiliated institutions, authors, and total citations. Results: The total number of citations for 100 articles was 73,483. Citations for individual articles ranged from 453 to 3,064, with a median of 588 (IQR: 341).The United States contributed the most papers (n = 70), followed by France and the United Kingdom (n = 5). Most articles, 67, were published prior to the 21 st century and only 3 were in the last 10 years. The most cited study was Malkin et al.’s Germ line p53 mutations in a familial syndrome of breast cancer, sarcomas, and other neoplasms with 3,064 citations. Of the top 10, 8 were published between 1978 and 1998. Journal of Clinical Oncology made the greatest number of contribution to the research on sarcoma with a total of 18 articles (citations = 12,166), followed by Cancer with 15 (citations = 9,052), and Proceedings of the National Academy of Sciences of the United States with 10 (citations = 8,431). The median Scopus CiteScore for publishing journals was 19.7, the highest being The Lancet (115.3) and The Iowa Orthopaedic Journal with the lowest score (1.5). Conclusions: Within the United States, the institutions producing the most literature were the NCI and Memorial Sloan Kettering Cancer Center. The majority of the 100 most cited studies are cited an average of 735 times, indicating that these sources are providing a substantial foundation for emerging research in the field. This begs the question of the quality and relevance of evidence in the literature, given the amount of citations. The Lancet produced literature with the highest journalistic impact, having a CiteScore of 115.3 based on Scopus metrics. While the majority of the 100 most cited pieces of literature (67%) on sarcomas were published prior the 21 st century, a small portion, eight, were produced in the last decade. This information could indicate either a lull in the frequency of research being conducted, or an effort on the part of institutions to create more substantial investigations that provide more valuable contributions to the field of research in sarcomas. We hope to continue seeing the field of sarcoma expand with new advances in its management.
Effectiveness and safety outcomes in patients with EBV<sup>+</sup> PTLD treated with allogeneic EBV-specific T-cell immunotherapy (tabelecleucel) under an expanded access program (EAP) in Europe.
Authors: Sylvain Choquet, Andrew Clark, Cécile Renard, Ben Uttenthal, Sridhar Chaganti, Ralf Ulrich Trappe, Patrizia Comoli, Xinyuan Duan, Baodong Xing, Charley Wu, Laurence Gamelin, Jan-Henrik Terwey, Anke Friedetzky, Daan Dierickx
Journal: Journal of Clinical Oncology (2023)

7521 Background: Pts with relapsed or refractory (r/r) EBV + post-transplant lymphoproliferative disease (PTLD) in Europe have had historically poor overall response rates and median overall survival (OS) with no approved treatment options. Tabelecleucel, an off-the-shelf, allogeneic EBV-specific T-cell immunotherapy has shown clinical benefit and favorable safety profile in the treatment of EBV + PTLD failing rituximab ± chemotherapy (Prockop EBMT 2021, ATC 2021, ASH 2022). Its recent European marketing authorization (EMA) represents the first approval of an allogenic T-cell immunotherapy globally. Methods: Atara Bio supported expanded access requests for tabelecleucel in Europe. Here we report updated effectiveness and safety data for r/r EBV + PTLD pts who provided consent for research between Sep 2020 and Dec 2022. Results: 74 EAP requests were received from 10 countries for pts with r/r EBV + diseases. 27 EBV + PTLD pts consented to secondary use of data and 24 pts had received ≥1 dose of tabelecleucel, including 4 pts with primary central nervous system (PCNS) PTLD. 16 of 24 (66.7%) PTLD pts achieved a partial (PR) (33.3%) or complete (CR) (33.3%) response, with median time to response (TTR) of 1.0 mo (0.8–2.2). Response rate for PCNS PTLD pts was 75% (1 CR, 2 PR). 1-yr OS Kaplan–Meier (KM) estimate rates were 73.7% (95% CI: 47.3, 88.3) overall, 87.5% in allogeneic hematopoietic stem cell transplant (HCT) and 66.5% in solid organ transplant (SOT), with a median follow-up time of 9.9 (2.4–13.9) and 6.0 (0.7–18.0) mo, respectively. Serious treatment-emergent adverse events (TESAEs) were reported in 7 (29.2%) pts, including 1 fatal event of disease progression. Predefined risks for tabelecleucel were reported in 3 pts; 1 (4.2%) SOT pt had a TESAE of liver transplant rejection (grade 2) and 2 (8.3%) HCT pts had non-serious TEAEs of chronic graft-versus-host disease (grade 1 and 2). No cases of cytokine release syndrome or tumor flare reaction were reported. No AEs were reported as related to tabelecleucel by the treating physician. Conclusions: These updated real-world results for pts with r/r EBV+ PTLD post-HCT or post-SOT treated in the European EAP continue to reinforce the favorable risk:benefit profile of tabelecleucel and are in line with clinical study data supporting its recent EMA approval. [Table: see text]
Intratumoral heterogeneity as a predictive biomarker in immunotherapy for advanced head and neck squamous cell carcinoma.
Authors: Juying Liu
Journal: Journal of Clinical Oncology (2023)

e18028 Background: Intratumoral heterogeneity (ITH) is associated with the poor prognosis in a variety of solid tumors, because of the therapeutic failure and drug resistance. However, we still lack understanding of the relationship between ITH and immunotherapy for advanced head and neck squamous cell carcinoma (HNSCC). Methods: We used the Bioconductor R package Maftools to analyze somatic variants of HNSCC from MSK-IMPACT-1611 study cohort (PMID: 30643254) with data from 68 patients. Then, a mutant-allele tumor heterogeneity (MATH) algorithm was used to measure ITH score. Finally, we analyzed the difference in the genomes, and the association with tumor mutational burden (TMB) between the ITH score high (ITH-H) and ITH score low (ITH-L) groups, and the effect of ITH on the prognosis of immunotherapy. Results: There was no significant difference in the high frequency mutated genes between the high ITH and low ITH groups. The genes with the highest mutation frequency in ITH-H group were TP53 (90.48%), TERT (47.62%), CDKN2A (38.1%), FAT1 (33.33%), NOTCH1 (28.57%), KMT2D (19.05%), APC (14.29%), and ASXL1 (14.29%), while the genes with the highest mutation frequency in ITH-L group were TP53 (44.68%), PIK3CA (38.3%), TRET (36.17%), FAT1 (21.28%), NOTCH1 (19.15%), KMT2C (17.02%), KMT2D (17.02%), and CDKN2A (14.89%). The median overall survival (mOS) of ITH-L group was significantly higher than that of ITH-H group (not reach versus 10 months, hazard ratio (HR) = 2.15, 95%CI 1.05−4.4, P = 0.032). There was no significant difference in median TMB levels between ITH-L and ITH-H groups (P = 0.55). The TMB high (TMB-H) patients had no significantly better mOS than the TMB low (TMB-L) group (HR = 0.54, 95%CI 0.25−1.16, P = 0.11). A pooled analysis of ITH and TMB show that the ITH-L+TMB-H group had significantly better improvement mOS than that in the ITH-L+TMB-L, ITH-H+TMB-H, and ITH-H+TMB-L group (HR = 0.71, 95%CI 0.13−1.35, P = 0.048). Conclusions: ITH may serve as a positive predictor of immunotherapy in patients with advanced HNSCC and is independent of TMB.
Examination of current status of cross-provincial border access for clinical trials for patients with cancer.
Authors: Claire Rim, Farwa Zaib, Kayla Touma, Mahmoud Hossami, Rhonda Abdel-Nabi, Dora Cavallo-Medved, Olla Hilal, Zoe Driedger, Devinder Moudgil, Milica Paunic, Renee Nassar, Roaa Hirmiz, Lee McGrath, Caroline M. Hamm
Journal: Journal of Clinical Oncology (2023)

e18661 Background: Clinical trials are the gold standard for establishing new and reliable treatment options. Even though 80% of cancer patients state that they would be interested in entering a clinical trial, only 3% of adults with cancer participate in clinical trials due to several challenges. Through a Clinical Trials Navigator program, we have curated clinical trials for approximately 243 patients and 7% have entered onto clinical trials. However, none of the patients were referred to trials outside of their home province due to a lack of clarity on the cross-border referral process. The goal of this study is to analyze the availability of patients for participating in out-of-province clinical trials in the presence of a lack of policy for provincial border referrals. Methods: This study was conducted by doing clinical trial searches for cancer patients using several clinical trial search engines such as ClinicalTrials.Gov, CanadianCancerTrials.com, ClinicalTrialsOntario, 3CTN, and Q-CROC. We also used a search engine to compare the number of clinical studies available in various cities for the four most common types of cancer in Canada. After this, an analysis was performed on over 243 clinical trial searches. Results: Out of the 18 patients we observed, most of them had potential out-of-province trials, but none of them joined out-of-province trials because of the lack of information regarding the process. Also, province disparity in trial availability was found for the most common cancers in Canada. The numbers of trials available in Ontario and Quebec are much higher than the number of trials available in PEI and Newfoundland which is almost zero or zero. The home treatment center of most of the patients involved in this study was Windsor Regional Hospital, and all of them were from Ontario. Among the patients that were referred, most of them were referred to Princess Margaret Cancer Centre in Toronto. Again, none of the patients were referred to cancer centers out of Ontario. Conclusions: In conclusion, our findings reveal the province disparity in the number of clinical trials available. The lack of policies that inform Canadians on how to cross provincial boundaries to enter a clinical trial prevents them from receiving the most needed cutting-edge treatments, compromising potential patient outcomes. Therefore, we need more clarity on policies for the cross-border referral process.
Addition of doxycycline to fluoroquinolones for bacterial prophylaxis in autologous stem cell transplantation for multiple myeloma.
Authors: Emma Guare, Joseph Cioccio, Kevin Rakszawski, Myles Nickolich, Seema Naik, Hong Zheng, Baldeep Wirk, Christopher Ehmann, David Claxton, Witold B. Rybka, Raymond J. Hohl, Joseph Mierski, Brooke Silar, Caitlin Vajdic, Jeffrey Michael Sivik, Cory Hale, Shin Mineishi, Kentaro Minagawa, Catharine I Paules
Journal: Journal of Clinical Oncology (2023)

e18732 Background: Autologous stem cell transplant (ASCT) is standard therapy for patients (pts) with multiple myeloma (MM), yet the risks of such treatment include neutropenic fever (NF) and bacteremia. Fluoroquinolones (FQs) are a mainstay of bacterial prophylaxis (ppx) of NF in ASCT at many transplant centers and reduce the incidence of bacteremia. Nevertheless, ppx regimens for ASCT are not standardized and variability exists even within single institutions. While antibacterial ppx decreases infections, antibiotic use can also cause toxicity, resistance, and microbiome disturbance. The addition of doxycycline (doxy) to FQs was previously linked to reduced NF and bacteremia when utilized for ppx in MM pts at our institution, leading some providers to incorporate doxy into their ppx regimens. However, our prior study introduced multiple confounders, including differing pre-transplant conditioning regimens between ppx groups. We sought to further compare the incidence of NF and bacteremia in MM pts receiving ppx with FQ alone and FQ-doxy during a time when ppx strategies varied but transplant conditioning was consistent between groups. Methods: This is a single institution retrospective review. We analyzed all medical charts in the ASCT database of MM pts treated at our institution between Jan 2016 and Dec 2021. The primary objective was to determine the effect of bacterial ppx on the rate of NF and bacteremia within 30 days of ASCT. Data was also collected on several pt characteristics. Results: Out of 341 pts with MM who underwent ASCT following melphalan (mel) conditioning, 121 received FQ (ciprofloxacin or levofloxacin) ppx and 220 received FQ-doxy ppx. Pt characteristics and outcomes of interest are shown in Table 1. NF developed in 71 (58.7%) and 103 (46.8%) pts in the FQ and FQ-doxy groups, respectively (p = 0.042). The odds of NF in FQ-doxy compared to FQ is 0.62 (95% CI 0.4, 0.97). Bacteremia developed in 7 (5.8%) and 6 (2.7%) pts of the FQ and FQ-doxy groups (p = 0.235). The odds of bacteremia in FQ-doxy compared to FQ is 0.46 (95% CI 0.15, 1.39). Documented bacteremia was infrequent, yet resistance profiles demonstrated FQ-resistant E. coli strains in the 7 total Gram-negative bacteremia cases and 5 extended-spectrum beta-lactamases. Conclusions: Overall, there were fewer cases of NF in the FQ-doxy ppx group than FQ, however there was no significant difference in the cases of bacteremia. This finding does not support the addition of doxy to FQ ppx at our institution and a future randomized controlled trial investigating appropriate ppx for ASCT is warranted. [Table: see text]
Hereditary breast and ovarian cancer syndrome: A misnomer?
Authors: Jessica M. Weiss, Muhammad Danyal Ahsan, Emily M. Webster, Sarah R. Levi, Murtaza Qazi, Benedict Harvey, Evelyn Cantillo, Kevin Holcomb, Eloise Chapman-Davis, Ravi N. Sharaf, Melissa Kristen Frey
Journal: Journal of Clinical Oncology (2023)

10594 Background: Germline pathogenic gene variants (PGV) in homologous recombination deficiency (HRD) genes are traditionally associated with breast, ovarian, pancreatic, prostate and melanoma skin cancer. Recent evidence suggests other cancers may also be associated with these genes. We analyzed the prevalence of somatic HRD mutations in common, traditionally non-hereditary breast and ovarian cancer (HBOC) associated incident cancers in the US. Methods: Data were collected from the American Association for Cancer Research’s (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) database version 13.0 via cBioPortal (http://genie.cbioportal.org). This is a publicly available, multi-institutional database of next-generation sequencing (NGS) genomic profiles of tumor samples. The database was queried for all cancers with at least 20,000 incident cases in 2022, as reported by the American Cancer Society, excluding well established HBOC associated cancers – breast, ovarian, prostate, pancreatic, melanoma. Frequencies of somatic PGVs were reported for nine HRD genes currently included in National Comprehensive Cancer Network (NCCN) management guidelines for HBOC: ATM , BARD1, BRCA1, BRCA2, BRIP1, CHEK2, PALB2, RAD51C and RAD51D. Results: A total of 78,285 tumor samples across 12 cancer types were included. At least 1 somatic HRD was found in 6.8% of all included tumors. At least 1 HRD PGV was most common in: Uterine Cancer (694/5,760, 12.1%), Non-Melanoma Skin Cancer (127/1,209, 10.5%), Bladder Cancer (462/4,605, 10.0%), Colorectal Cancer (1306/14,625, 8.9%) Non-Hodgkin’s Lymphoma (5/58, 8.6%), Esophagogastric Cancer (356/4,649, 7.7%), Hepatobiliary Cancer (219/3,325, 6.6%), Lung Cancer (1,480/23,621, 6.3%), Kidney Cancer (113/2,564, 4.4%), Brain Cancer (420/10,206, 4.1%), Thyroid Cancer (89/2,246, 4.0%) and Leukemia (80/5,417, 1.5%). The most common PGVs across all cancer types were BRCA1/2 and ATM (Table). Conclusions: A pan-cancer analysis using NGS data demonstrates a substantial rate of somatic HRD PGVs in common, traditionally non-HBOC associated cancers in the US. These data raise the possibility that germline pathogenic variants in HRD genes could be associated with several more cancers than currently known, underscoring the need for studies evaluating risks of the aforementioned cancers in germline PGV carriers. Additionally, these findings present opportunities for trials evaluating the efficacy of HRD-targeting therapies in these cancers. [Table: see text]
Association of patient and tumor characteristics with outcomes in young patients with head and neck squamous cell carcinoma (HNSCC).
Authors: Ronan Wenhan Hsieh, William E. Gooding, Marci Lee Nilsen, Mark Kubik, Zahra Rahman Kelly, Shaum Sridharan, Heath Devin Skinner, Uzoma K. Iheagwara, Jose Zevallos, Umamaheswar Duvvuri, Seungwon Kim, Robert L. Ferris, Dan Paul Zandberg
Journal: Journal of Clinical Oncology (2023)

e18054 Background: HNSCC is increasingly being diagnosed in a younger population, with a variable prognosis. While studies have evaluated outcomes in young compared to older patients, evaluation of prognostic factors specifically in younger patients, that may help guide treatment decisions, is needed. Therefore, we conducted a retrospective study to investigate the association of patient and tumor characteristics with disease specific survival (DSS) in HNSCC patients ≤45 years old (yo). Methods: Patients treated at the University of Pittsburgh Medical Center from January 1, 2007 to June 30, 2020, that were ≤45 yo at time of diagnosis with HNSCC without distant metastatic disease, were included. Those who received treatments at other institutions and who had no follow-up after index treatments were excluded. Patient demographics, social history, tumor pathology and treatment course were collected. The primary endpoint of DSS was defined as the interval between the time of pathologic diagnosis and the time of cancer-related death. Proportional hazards regression was applied separately for surgically and non-surgically treated patients. A multivariate analysis was conducted for surgically treated patients only. Results: 230 patients were included. Median age was 42, 73% male, 45% oral cavity primary, 35% oropharynx (89% Human papillomavirus positive), 14% larynx, 69% were smokers, and 73% received combined modality therapy. 35% of patients had a recurrence with the majority locoregional only (61%). Median DSS was not reached. The 5 year DSS was 73% (95% CI 67% to 80%). There was no difference in DSS between surgically treated (n = 169) and non-surgically treated (n = 61, p = 0.94) patients. For surgically treated patients, univariate analysis showed significantly worse DSS in those with higher pathologic T and N stages, positive margins, perineural invasion (PNI), extranodal extension (ENE), and negative HPV status. For non-surgically treated patients, only negative HPV status was associated with significantly worse DSS (p = 0.034). In the multivariate analysis for surgical treated patients, which included all significant characteristics from univariate analysis, pathologic T and N stage, positive margins, (HR 4.92, 95% CI 1.98-12.25, p = 0.006) and PNI (HR 2.66, 95% CI 1.17-6.08, p = 0.02) were significantly associated with worse DSS. Conclusions: Pathologic T and N stage, positive margins, and PNI are independently associated with significantly worse DSS in surgically treated HNSCC patients aged ≤45. Compared with classic prognostic factors seen in the overall population with HNSCC, PNI may be a uniquely strong prognostic factor in younger-aged HNSCC patients.